Observations in a number of laboratories including my own have demonstrated that animal cells in tissue culture could be made to grow under conditions that would allow them to retain characteristics typical of the tissue from which they were derived. In other words, cartilage cells can be grown in tissue culture and would produce typical cartilage matrix products, pituitary cells would produce pituitary hormones, etc. Among the products which were of interest to our laboratory were a group of complex saccharides normally considered as secretory products of cells in that they are found in the extracellular matrix in which fibrous and cellular elements are resident. This class of compounds has about six representatives with certain common features including aspects of their molecular size and high negative charge. This latter property is most often used in isolation and identification of this particular group.
A study was then carried out wherein direct comparison could be made between a normal cell line and the same cell line after infection with a viral agent which rendered the cell tumorigenic. This work was reported in Proc. Nat. Acad. Sci., USA, Vol. 70, No. 1, pp. 53 - 56, January 1973.
It was found that there was no qualitative difference between the saccharide products but rather a quantitative difference occurred upon viral transformation insofar as the synthesis of one of the characteristic saccharides was concerned. This type of quantitative change is useful for studies in a cell culture system but could never be used for any purpose in animal studies because the particular product involved is normally found in most tissues of the body, is non-antigenic and cannot under any circumstances be considered characteristic of the tumor cell. Nonetheless, the qualitative differences were of interest and were found to be quite general. The conclusion could be drawn that conversion of a cell line by virus transformation involves at least a change in the pattern of complex saccharide synthesis.
As reported in Biochemistry (1974) Vol. 13, p. 1233, my laboratory carried out a similar series of experiments with the B16 mouse melanoma cells and a control population of normal melanocytes derived from the iris of mice. The differences observed between the melanoma cells and the control population were somewhat more striking than those observed for the normal and virus transformed pairs referred to above. These differences can be briefly summarized as follows:
1. There was both a qualitative and a quantitative difference in the production of complex saccharides when the tumor cells were compared with their normal counterparts. PA1 3. A sulfated polysaccharide of unusually high molecular weight was produced by the tumor line but was absent in the normal cells.
2. In particular, a major product of the normal cells, hyaluronic acid, was not produced at all by the tumorigenic line.
With regard to the sulfated polysaccharide, it is important to note that the compound produced differs from normal components of tissue only in its molecular size and not in its molecular architecture. That is, the structure of the saccharide was identical to the structures normally found in tissue materials but the size was somewhat larger. Once again, this is suitable for studies under cell culture conditions but is essentially useless as a diagnostic technique since the compound in question is rapidly metabolized by a variety of cells in host animals. Should such a compound appear in the circulation, it would rapidly be cleared and digested by liver cells, kidney cells, fibroblasts, etc. Therefore, as a diagnostic technique, the presence or production of this saccharide by the tumor cells offered no utility, not only for the reason mentioned above but also because the compound itself is non-antigenic.
In a publication in Cancer Research, 36, 424 - 431, February 1976 I reported the results of a complex saccharide study of human cells which in many respects are similar to those obtained in the mouse. The human melanoma cells produce less hyaluronic acid than the control melanocytes and a high molecular weight sulfated polysaccharide similar to that produced by the mouse cells.
Further studies of the mouse system revealed the presence of an unusual glycoprotein. Accordingly, an effort was made to further understand the nature of the mouse glycoprotein insofar as its properties, structural chemistry and biological function could be defined. Many of the chemical properties of the molecule are described in my paper in Biochemical and Biophysical Research Communications, Vol. 70, No. 1, May 1976. The presence of an unusual glycoprotein in the human melanoma cells or its production by them is not reported in this publication although it may be alluded to on page 144 of said paper as unpublished results of my laboratory.